Ion channel activity of the BH3 only Bcl-2 family member, BID

Sharon L. Schendel, Rustam Azimov, Krzysztof Pawłowski, Adam Godzik, Bruce L. Kagan, John C. Reed

Research output: Contribution to journalArticlepeer-review

158 Scopus citations

Abstract

BID is a member of the BH3-only subgroup of Bcl-2 family proteins that displays pro-apoptotic activity. The NH2-terminal region of BID contains a caspase-8 (Casp-8) cleavage site and the cleaved form of BID translocates to mitochondrial membranes where it is a potent inducer of cytochrome c release. Secondary structure and fold predictions suggest that BID has a high degree of α-helical content and structural similarity to Bcl-X(L), which itself is highly similar to bacterial pore-forming toxins. Moreover, circular dichroism analysis confirmed a high α-helical content of BID. Amino-terminal truncated BIDA1-55, mimicking the Casp-8-cleaved molecule, formed channels in planar bilayers at neutral pH and in liposomes at acidic pH. In contrast, full- length BID displayed channel activity only at nonphysiological pH 4.0 (but not at neutral pH) in planar bilayers and failed to form channels in liposomes even under acidic conditions. On a single channel level, BIDA1-55 channels were voltage-gated and exhibited multiconductance behavior at neutral pH. When full-length BID was cleaved by Casp-8, it too demonstrated channel activity similar to that seen with BIDA1-55. Thus, BID appears to share structural and functional similarity with other Bcl-2 family proteins known to have channel-forming activity, but its activity exhibits a novel form of activation: proteolytic cleavage.

Original languageEnglish (US)
Pages (from-to)21932-21936
Number of pages5
JournalJournal of Biological Chemistry
Volume274
Issue number31
DOIs
StatePublished - Jul 30 1999

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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